OnKure Announces IND Clearance by U.S. FDA Enabling Phase 1 Initiation for its Mutant Selective PI3Ka inhibitor, OKI-219

On January 4, 2024 OnKure, Inc. reported that the U.S. Food and Drug Administration (FDA) has cleared the Investigational New Drug (IND) application of OKI-219, a potential best-in-class, mutant selective PI3Ka H1047R inhibitor, for clinical evaluation (Press release, OnKure, JAN 4, 2024, View Source [SID1234638979]). H1047R is the most common mutation in PI3Ka, being found in 15% of breast cancer and 4% of cancers overall.

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There is a significant need for improved therapies targeting PI3Kα with safer and more effective drugs. OKI-219 is a highly selective inhibitor of PI3Ka H1047R, with over 100-fold selectivity for the wild-type enzyme, potentially sparing on-target toxicities that arise from inhibition of the wild-type form of the protein in normal tissues. OKI-219 shows strong, single-agent activity, including regressions at low doses in multiple PI3Ka H1047R xenograft models that are heterozygous for PI3Ka H1047R, the most common profile seen clinically for this mutation, and supporting the potential activity of highly mutant-selective inhibitors. Notably, in preclinical models, OKI-219 shows no evidence of toxicities related to PI3Ka wild-type inhibition as measured by markers of hyperglycemia, even at doses that are >15x higher than minimally active doses for antitumor activity.

Mutational activation of PI3Kα is associated with lower activity of both estrogen receptor (ER)-targeted and HER2-targeted agents in breast cancer. OKI-219 shows synergistic activity in combination with selective estrogen receptor degraders (SERDs), overcoming SERD resistance and driving strong regressions. Similarly, the combination of OKI-219 + tucatinib drives strong regressions in models of HER2+/ PI3Ka H1047R breast cancer that are resistant to HER2- inhibitors.

OnKure plans to initiate a first-in-human clinical trial, OKI-219-101 (PIKture-01), in the first quarter of 2024 that will include a dose escalation in patients with advanced solid tumors harboring the PI3Ka H1047R mutation. Subsequent evaluation of OKI-219 in combination with the SERD fulvestrant in ER+/ PI3Ka H1047R advanced breast cancer, and with the HER2-monoclonal antibody trastuzumab in HER2+/ PI3Ka H1047R advanced breast cancers will follow.

About PI3Ka and OKI-219

PI3Ka is the most frequently mutated oncogene in cancers, and PI3Ka H1047R is the most common mutation in this gene, being found in 15% of breast cancer and 4% of cancers overall. While novel drugs targeting PI3Ka have been approved, the lack of mutant selectivity of these therapeutics drives considerable on-target toxicity by inhibiting the normal version of this protein in various tissues. To address this challenge, OnKure is discovering and developing a platform of highly mutant-selective PI3Ka inhibitors with the goal of improving efficacy and safety with molecules that fully inhibit the mutant oncogene while sparing the wild-type enzyme in normal tissues. OKI-219 is a potential best-in-class, orally bioavailable, highly selective inhibitor of PI3Ka H1047R with over 100-fold selectivity for the mutated form of the enzyme compared to wild-type. OnKure believes that the wild-type sparing properties of OKI-219 should significantly improve the activity and safety relative to currently approved agents. OKI-219 is currently in Phase 1 of clinical development in solid tumor patients with PI3Ka H1047R mutations.

Oncolytics Biotech® Recaps 2023 Accomplishments, Provides Outlook for 2024

On January 4, 2024 Oncolytics Biotech Inc. (NASDAQ: ONCY) (TSX: ONC), a clinical-stage immunotherapeutics company focused on oncology, reported on significant 2023 accomplishments and reported corporate priorities and anticipated clinical development milestones for 2024 (Press release, Oncolytics Biotech, JAN 4, 2024, View Source [SID1234638978]).

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Overview: "2023 was an outstanding year for Oncolytics and the development of pelareorep as a potential cancer therapy. To date, we have studied pelareorep in more than 1,100 patients, and it has been shown to be well-tolerated with mild side effects. Promising clinical and translational results from our Phase 2 programs and mechanism of action learnings from a wide range of tumor types, as detailed below, provided consistent data and efficacy signals with durable responses that support the use of pelareorep as an immunotherapeutic agent, either as a monotherapy or in combination with other agents. These data readouts from multiple clinical studies at numerous sites and from diverse cancer indications that are clinically important make a compelling argument for pelareorep as a true backbone immunotherapy with the potential to help countless patients across a range of tumors," said Dr. Matt Coffey, President and Chief Executive Officer of Oncolytics. "We believe our cash balance and strong data, supported by our active business development program, position us well for 2024."

Positive Clinical and Translational Data: "Positive, early results from the Phase 1/2 GOBLET study in three gastrointestinal cancers – pancreatic, anal, and colorectal – showed that the combination of pelareorep and atezolizumab produced clinically meaningful improvements in response rates and survival timelines that are notably improved compared to historical results with no toxicity concerns. Translational data from studies in solid tumors, breast, pancreatic, and colorectal cancers showed that treatment with pelareorep remodels the tumor microenvironment and stimulates tumor-directed immune responses, affirming its mechanism of action as an immunotherapeutic agent. Together, these data provide a strong foundation to support advancing pelareorep into registrational-track studies, starting in 2024," continued Dr Coffey.

2024 Outlook: Dr. Coffey concluded by saying, "Looking ahead to 2024, we expect to initiate the first Phase 3 study for pelareorep in pancreatic cancer. The transition to a late-stage biopharmaceutical company will mark an important inflection point for investors, clinical collaborators and potential partners by providing a line of sight towards the path to regulatory approval and achieving our mission of developing pelareorep as an immunotherapeutic agent for cancer. We are excited to launch a new Phase 1/2 pancreatic cancer study investigating, for the first time, pelareorep in combination with modified FOLFIRINOX (mFOLFIRINOX). Finally, our discussions with regulators on a pivotal Phase 3 trial have been productive to date, and we expect to provide guidance on the registration path for metastatic breast cancer in the first half of 2024. We look forward to updating our stakeholders on our progress as the year unfolds."

Immunotherapeutic Mechanism of Action: Thomas Heineman, M.D., Ph.D., Chief Medical Officer at Oncolytics, said, "Translational data from multiple studies in 2023 have helped define pelareorep’s role in shaping the tumor microenvironment and have provided a better understanding of its ability to induce the expansion of T cell populations. Notably, the positive association between tumor response and TIL clone expansion could become a useful marker of clinical outcomes in future studies and during patient care. Moreover, these findings further distinguish pelareorep’s mechanism of action from that of other immunotherapeutic agents and provide support for its immunologic effects, which are largely driven by the introduction of its double-stranded RNA genome into cancer cells."

Financial Strength and Partnering Outlook: Kirk Look, Oncolytics’ Chief Financial Officer, commented, "Our $40 million cash balance as of September 30, 2023, and the grant funding from The Pancreatic Cancer Action Network (PanCAN) provides us with over 12 months of runway to support our operations, including the initiation of our first Phase 3 study and the BRACELET-1 survival data. We continue to have active conversations with potential partners and work diligently with clinical collaborators, including Roche and Pfizer. We believe the positive, extended dataset, including continued and durable responses, survival results, and translational observations, will provide potential partners with a well-defined and unique target product profile that will add to our discussions."

Anticipated Milestones are expected to include:

•H1 2024: Guidance on the registration path for HR+/HER2- mBC (metastatic breast cancer)
•H1 2024: Initiation of the PanCAN-supported Phase 2 Pancreatic Ductal Adenocarcinoma (PDAC) trial incorporating mFOLFIRINOX +/- atezolizumab and pelareorep
•Mid-2024: Initiation of the adaptive Phase 3 trial for pelareorep in PDAC
•Overall survival results from the BRACELET-1 study
•Expand enrollment following achievement of success criteria from the GOBLET Phase 1/2 study anal cancer cohort

Highlights of Oncolytics Biotech’s 2023 Achievements:

HR+/HER2- Metastatic Breast Cancer Program and the BRACELET-1 study
•Promising Randomized Phase 2 Data Readout Supports Previous Near Doubling of Median Overall Survival: Data presented at the 2023 American Society of Clinical Oncology (ASCO) (Free ASCO Whitepaper) Annual Meeting showed that pelareorep in combination with paclitaxel (cohort 2) resulted in a near tripling of confirmed overall response rate, a 50% increase in median progression-free survival, and a hazard ratio of 0.29 (link to the PR) compared to paclitaxel monotherapy (cohort 1).

Overall survival (OS) data continues to mature since multiple patients continue to be followed for survival in the pelareorep + paclitaxel cohort. Positive results would provide Oncolytics with two successful randomized Phase 2 studies showing a meaningful OS benefit for pelareorep. The data reported so far supports the initiation of a pivotal study in mBC and makes the case for an overall survival and progression-free survival dual endpoint in a registrational trial, which could substantially reduce the time to potential approval.

Gastrointestinal Cancers and the GOBLET study cohorts
•Pancreatic Cancer Survival Data Reported at ESMO (Free ESMO Whitepaper) Supports Decision to Move to Phase 3: Updated data presented at the European Society for Medical Oncology (ESMO) (Free ESMO Whitepaper) Congress 2023 showed a 62% objective response rate, nearly triple what has been seen in historical control trials. In addition, interim survival data, including median progression-free survival and median overall survival timelines, exceed historical control trials by 25% or more (link to the PR, link to the poster). Patients in this single-arm, open-label study with advanced PDAC were treated with pelareorep, atezolizumab, gemcitabine, and nab-paclitaxel.

We continue to follow the survival of several patients in this cohort as well as patients from the GOBLET study with third-line colorectal cancer, which also met the pre-defined success criteria (link to the PR, link to the poster). Having received Fast Track designation from the FDA for the treatment regimen of pelareorep, atezolizumab, gemcitabine, and nab-paclitaxel in metastatic PDAC patients last year, we were very pleased to report additional promising data for this combination, paving the way to initiate our adaptive Phase 3 trial which will now be conducted by Oncolytics, building on the positive feedback from our work with PanCAN.

Also, thanks to a US$5 million grant from PanCAN, we will examine the potential of pelareorep in combination with mFOLFIRINOX +/- atezolizumab. With these data plus the results from the adaptive Phase 3 PDAC study (pelareorep + gemcitabine + nab-paclitaxel + atezolizumab), we hope to show efficacy data for pelareorep in combination with the two most commonly used treatment regimens for pancreatic cancer patients, which could help pave the way for future broad adoption by physicians and impact a substantial number of patients.

•Anal Cancer Data – Positive Early Results in an Underserved Patient Population: Data presented at the 2nd International Multidisciplinary Anal Cancer Conference (IMACC 2023) achieved the pre-defined Simon-two-step success criteria and showed a near tripling of objective response rates compared to historical control trials in addition to a complete response (link to the PR, link to the poster). Patients in this single-arm, open-label study with second-line, unresectable squamous cell carcinoma of the anal canal (SCCA) were treated with pelareorep and atezolizumab, marking an exciting signal of efficacy in an indication where checkpoint inhibitors have had limited impact historically, and there are few treatment options.

Having met the success criteria for efficacy for this cohort, we will work closely with AIO-Studien-gGmbH (AIO), which is managing the GOBLET study, to expand the number of patients who can be treated and, hopefully, accelerate the enrollment process. With continued positive data, this could become another high-priority indication for the company.

Other Opportunities: Preclinical data published in Science Translational Medicine (link to the PR) from studies in murine tumor models showed that combining CAR T cells with pelareorep improved CAR T cell persistence and efficacy in solid tumors. An intravenous boost of pelareorep enhanced this effect and led to tumor cures in >80% of cases. We believe there is a significant opportunity here as CAR T cell therapy is currently only effective in hematological cancers, and solid tumors are the vast majority of cancers diagnosed each year. While we do not have an active program underway, we continue to have discussions on the best way to advance this effort.

I would like to take this moment to wish everyone a Happy New Year and thank our shareholders for their support. We look forward to providing additional positive updates in 2024.

Kineta to Participate in the 13th Annual LifeSci Partners Corporate Access Event

On January 4, 2024 Kineta, Inc. (Nasdaq: KA), a clinical-stage biotechnology company focused on the development of novel immunotherapies in oncology that address cancer immune resistance, reported that management will participate in the 13th Annual LifeSci Partners Corporate Access Event, taking place January 8-10, 2024 at the Beacon Grand Hotel in San Francisco, California during J.P. Morgan week (Press release, Kineta, JAN 4, 2024, View Source;utm_medium=rss&utm_campaign=kineta-to-participate-in-the-13th-annual-lifesci-partners-corporate-access-event [SID1234638977]).

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"We look forward to participating in the LifeSci Corporate Access Event and to hosting in-person meetings with investors, strategic partners, analysts and other stakeholders", said Shawn Iadonato, Ph.D., Chief Executive Officer of Kineta. "2024 has the potential to be a substantial growth year as we continue to make significant progress on the clinical development of KVA12123, our novel VISTA immunotherapy."

During the event, the Kineta management team will host one-on-one meetings on January 8th and 9th, 2024 and will be available to present a corporate overview and provide an update on the VISTA-101 Phase 1/2 clinical trial evaluating KVA12123 in patients with advanced solid tumors.

To schedule a meeting, please register at LifeSci Partners Corporate Access Event 2024.

Integral Molecular Enters Into Exclusive Antibody License With Seismic Therapeutic

On January 4, 2024 Integral Molecular, a leading biotech company specializing in antibody discovery against undruggable protein targets, reported that it has entered into an antibody license agreement with Seismic Therapeutic (Press release, Integral Molecular, JAN 4, 2024, View Source [SID1234638976]). Under the terms of the agreement, Integral Molecular will provide an exclusive license to Seismic Therapeutic for a collection of fully humanized, highly specific, preclinical antibodies to add to their platform, library, and pipeline of molecules in the immunology space. Seismic Therapeutic will assume full responsibility for all research, development, and commercialization activities related to these antibodies.

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The antibodies licensed by Seismic Therapeutic were identified using Integral Molecular’s MPS Antibody Discovery platform. This platform is built upon the company’s 20+ years of experience in working with the most challenging protein targets and ability to deliver preclinical lead candidate molecules. Unique aspects of this platform include the use of advanced immunization strategies including combinations of RNA, DNA and protein boosting via Lipoparticles, and evolutionarily divergent host animals (chickens) capable of generating diverse panels of antibodies against highly conserved targets.

"We are thrilled that Seismic chose Integral Molecular as a partner for their antibody discovery efforts," said Ross Chambers, PhD, VP of Antibody Discovery at Integral Molecular. "Using chickens as immunization hosts was important for Seismic’s project, as conventional approaches like mouse immunization would not have produced the diverse antibodies needed for their program. We wish Seismic Therapeutic much success as they continue to develop these antibodies."

Inspirna to Present at the 42nd Annual J.P. Morgan Healthcare Conference

On January 4, 2024 Inspirna, Inc., a clinical stage biopharmaceutical company developing first-in-class cancer therapeutics, reported that Chief Executive Officer Dr. Usman "Oz" Azam, M.D., will participate in a corporate presentation at the 42nd Annual J.P. Morgan Healthcare Conference on Thursday, January 11, 2024 at 8:30am PT / 11:30am ET (Press release, Inspirna, JAN 4, 2024, View Source [SID1234638975]).

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